Concentric Analgesics Announces Positive Topline Results from Phase 2 Clinical Trial of CA-008 in Bunionectomy

Clinically Meaningful Reductions in Pain Lasting Through One Week vs. Active Control
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50% Reduction in Opioid Use with 26% of Patients Opioid Free For 28 Days

November 8, 2018

Concentric Analgesics, Inc., a clinical-stage biopharmaceutical company focused on developing and commercializing novel, non-opioid pain therapeutics, today announced positive topline results from its Phase 2 clinical trial of CA-008, a first-in-class, non-opioid therapeutic.   The primary objective of the study, conducted in patients undergoing bunionectomy, was to demonstrate the efficacy of CA-008 over 96 hours, with secondary endpoints in opioid consumption, safety and pharmacokinetics.

The study showed that CA-008, administered at a dose of 4.2 mg, achieved statistically significant and clinically meaningful reductions in area under the curve (AUC) for pain intensity from 0 to 96 hours (33%, p=0.005), as well as from 0 to 168 hours (32%, p<0.05, at rest), compared to the control group, with all study patients receiving a standard of care which included an intraoperative bupivacaine Mayo block, IV ketorolac and IV acetaminophen.

Importantly, the 4.2mg dose of CA-008 reduced opioid consumption by 50% from 0 to 96 hours (p=0.0019) as compared to the control group, with 26% of patients being opioid free from 0 to 96 hours vs. 5% in the control group (p=0.039), an effect that was maintained throughout 28 days.  Further, post-hoc analysis revealed that 39% of patients receiving the 4.2mg dose of CA-008 did not require any opioids after the initial 24 hours, compared to 8% in the control group (p=0.0075).  CA-008 was well tolerated at all dose levels compared to the control group.

“The long-lasting reductions in pain scores and significant decreases in opioid use are exceptional, particularly as CA-008 was evaluated against a control group that received a real-world standard of care, which included perioperative bupivacaine, acetaminophen and an NSAID,” said Jean-Louis Horn, MD, Chief, Division of Regional Anesthesia and Acute Pain Medicine at Stanford University.

“Postoperative pain remains a major problem for surgical patients, and there have been few non-opioid therapeutic advances over the past decade.  CA-008, with its novel mechanism of action, has the potential to become the primary site-specific analgesic for post-surgical pain,” said Tong J. Gan, MD, Chairman, Department of Anesthesiology, Stony Brook University and founding President of the American Society for Enhanced Recovery.

Study Design
The randomized, double-blind, placebo-controlled study enrolled 147 patients undergoing bunionectomy and compared the safety and efficacy of CA-008 to a saline control.  During surgery, all patients received a standard of care that included a Mayo block (bupivacaine HCl 0.5%), IV ketorolac and IV acetaminophen.  The study was comprised of three arms receiving CA-008 0.7mg (n=36), 2.1mg (n=36) and 4.2 mg (n=38) and a standard-of-care control arm (n=37).  CA-008, a prodrug of capsaicin in an aqueous solution, was administered via wide infiltration at the surgical site.  The primary efficacy endpoint of the Phase 2 study was reduction in pain for AUC 0-96h, with key secondary endpoints including pain reduction over one week post-surgery and opioid consumption.

Efficacy Results
Patients were evaluated for pain intensity over 96 hours (primary efficacy endpoint) using the standard Numerical Rating Scale (NRS), as measured by the area under the curve (AUC).   Key secondary endpoints that were evaluated included opioid consumption, pain intensity over two weeks at rest and with ambulation, along with standard safety measures and PK sample collections.

At the highest dose of 4.2 mg, CA-008 showed statistically significant and clinically meaningful results, including:

  • 33% reduction of pain for AUC 0-96h (p=0.005).

  • 26% of patients were opioid free 0-96h (p=0.039), compared with 5% in the control group, an effect that was maintained throughout the full 28-day observation period.

  • 50% reduction in opioid consumption 0-96h (p=0.0019).

  • 32% reduction of pain for AUC 0-168h (one week), at rest (p=0.0167) and 25% reduction with ambulation (p=0.0386).

Post-hoc analysis revealed that 39% of patients did not require opioids after 24 hours, compared to 8% in the control group (p=0.0075).

Safety Results

  • All three doses of CA-008 were determined to be safe and well tolerated with 85% of adverse events deemed not related to study treatment and most deemed to be “mild” or “moderate” in severity.

  • There were no serious adverse events (SAEs) in the CA-008 dose groups.

  • There were no meaningful differences in wound healing, x-ray findings or local neurosensory assessments between treatment groups and control.

“Today’s results confirm CA-008’s unique and compelling therapeutic profile and its ability to provide clinically relevant reductions in pain and opioid use that matter to physicians and patients,” said Frank Bellizzi, DMD, Chief Executive Officer of Concentric Analgesics. “Combined with the FDA’s recent granting of Breakthrough Therapy Designation for CA-008, these results provide further support and momentum as we continue to advance a broad-based development program to rapidly bring CA-008 to market.”

The Company expects to present complete data, including pharmacokinetics and full 28-day follow-up results from the Phase 2 clinical trial at upcoming scientific meetings in 2019. 

Based on the positive results of the bunionectomy study, the Company plans to immediately initiate Phase 2 efficacy studies with CA-008 in additional surgical models, including abdominoplasty and total knee arthroplasty.  The Company is also scheduling a multi-disciplinary meeting with FDA to discuss its current CA-008 development plan under Breakthrough Therapy Designation.

About Opioid Addiction & Post-Surgical Pain
Opioid addiction in the United States has reached epidemic proportions, destroying families, lives and communities throughout the country.  According to the Centers for Disease Control and Prevention, approximately 70,000 Americans died from opioid overdoses in 2017, a 10% jump from 2016 – and more than the total number of U.S. military deaths in all 15 years of the Vietnam war. New approaches for preventing this insidious disease are imperative, including in the post-surgical setting, which can be an unsuspecting gateway to prescription pain medicine abuse and beyond. A 2016 US News & World Report revealed that one in 10 patients report becoming addicted or dependent on opioids following surgery. With more than 100 million surgeries being performed in the U.S. in 2017, 30 million of which require post-surgical pain management with non-over the counter (OTC) pain medications, the mandate to develop safe and effective non-opioid alternatives is clear.

About CA-008
Concentric Analgesics’ lead product candidate for post-surgical pain is a first-in-class therapeutic that rapidly converts to capsaicin, a potent TRPV1-agonist. Unlike local anesthetics, CA-008 selectively desensitizes pain-conducting nerve fibers without producing numbness or weakness. CA-008, injected during surgery, has the potential to reduce and in some patients eliminate the need for opioids in the postsurgical recovery period. The compound is designed to provide clinically meaningful pain relief for a week or more resulting in quicker return to normal activities.

About Concentric Analgesics
Concentric Analgesics is a clinical-stage, biopharmaceutical company focused on developing and commercializing novel, non-opioid pain therapeutics. The Company’s portfolio of proprietary TRPV1-agonist prodrugs is designed to provide long-lasting, selective pain relief after a single local injection. Concentric has three active programs for multiple indications with significant unmet need: post-surgical pain, osteoarthritis and chronic refractory pain. For more information, please visit the Company’s website at: www.concentricanalgesics.com.

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